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CompletedNCT03200782Hypo-BEARUpdated Oct 24, 2018

Postprandial Hypoglycemia in Patients After Bariatric Surgery With Empagliflozin and Anakinra - The Hypo-BEAR-Study

An interventional study of Empagliflozin and Anakinra in Postprandial Hypoglycemia, Bariatric Surgery and Late Dumping Syndrome, sponsored by University Hospital, Basel, Switzerland. Completed at 1 site in Switzerland. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2018-10-24.

Sponsored by University Hospital, Basel, Switzerland · Not applicable, Interventional, and Diagnostic

Phase
Not applicable
Study type
Interventional
Enrollment
12
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

The purpose of the study is to investigate whether hypoglycaemia observed after food intake in bariatric patients can be either influenced by an SGLT2 inhibitor, empagliflozin, or via inhibition of inflammation with an human interleukin-1 receptor antagonist (IL1-RA, anakinra).

Read the detailed description

Postprandial hypoglycemia also referred as late-dumping after bariatric surgery can be clinically asymptomatic but also life-threatening. The exact mechanisms leading to postprandial hypoglycemia are not fully understood and therapeutic options are limited and often accompanied with reduced life-quality and weight gain.

In this study, prospective, randomly selected and double-blinded treatment is performed to investigate the effect on postprandial hypoglycemia. A total of 12 subjects participate in the study. After a screening date, three study dates will be performed. Participation in the study usually takes two weeks, but can also be extended to three weeks in individual cases. The University Hospital Basel will be the only test center in this study.

In order to check whether the increase in blood glucose after food intake and subsequent excessive reaction of the body followed by hypoglycaemia patients receive either anakinra as a subcutaneous injection 3h or empagliflozin as a tablet 2 h before a liquid standardized test meal. On one study day only subcutaneous and oral placebo control will be used.

At the beginning of each study date as well as at the time of the test meal several blood samples will be taken to evaluate blood glucose and blood glucose-influencing parameters (insulin / C-peptide, intestinal hormones, inflammatory parameters such as C-reactive protein, IL1beta and IL1-receptor agonist as well as macrophage and t-lymphocyte subpopulations) will be controlled. Questionnaires for dumping symptoms (Dumping Rating scale, Sigstad Score) and hypoglycemia testing with mini-mental test, stanford sleepiness scale and Edinburgh Hypoglycemia Scale will be performed repetitively.

02

Conditions studied

  • Postprandial Hypoglycemia
  • Bariatric Surgery
  • Late Dumping Syndrome

Keywords

  • postprandial hypoglycemia
  • bariatric surgery
  • late dumping syndrome
  • anakinra
  • empagliflozin
  • SGLT2 inhibitor
  • IL-1Beta
  • IL1
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Patients after roux-y-gastric bypass or biliopancreatic diversion with documented hypoglycemia, i. e. ≤ 2.5 mmol/l and hypoglycaemic symptoms.
  • For subjects with reproductive potential, willingness to use contraceptive measures adequate to prevent the subject or the subject's partner from becoming pregnant during the study

Exclusion criteria

Exclusion Criteria:

  • Signs of current infection
  • Use of any investigational drug in the last four weeks prior to enrolment
  • Use of any anti-diabetic drugs
  • adrenal insufficiency and/or substitution with glucocorticoids
  • Neutropenia (leukocyte count \< 1.5 × 109/L or absolute neutrophil count (ANC) \< 0.5 × 109/L)
  • Anemia (hemoglobin \< 11 g/dL for males, \< 10 g/dL for females)
  • Clinically significant kidney or liver disease (creatinine > 1.5 mg/dL, aspartate aminotransferase (AST)/alanine aminotransferase (ALT) > 2 × ULN, alkaline phosphatase > 2 × ULN, or total bilirubin [tBili] > 1.5 × ULN)
  • Current immunosuppressive treatment or documented immunodeficiency
  • Uncontrolled congestive heart failure
  • Uncontrolled malignant disease
  • Currently pregnant or breastfeeding
  • known lactose intolerance
04

Study design

Phase
Not applicable
Primary purpose
Diagnostic
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Double (Participant, Investigator)
Enrollment
12 participants (actual)

Study arms

  • Placebo comparator
    Placebo-Placebo

    subcutaneous placebo (0.67 ml of 0.9% sodium chloride) 3 hours before the test meal and an oral placebo (winthrop tablet) 2 hours before the test meal will be administered by an Independent nurse to the blinded patient

    Other: oral placebo (winthrop tablet) · Other: subcutaneous placebo (0.67 ml of 0.9% sodium chloride)

  • Active comparator
    Investigational Drug A Empagliflozin

    subcutaneous placebo (0.67 ml of 0.9% sodium chloride) 3 hours before the test meal and an 10mg of empagliflozin 2 hours before the test meal will be administered by an independent nurse to the blinded patient

    Drug: Empagliflozin · Other: subcutaneous placebo (0.67 ml of 0.9% sodium chloride)

  • Active comparator
    Investigational Drug B Anakinra

    subcutaneous injection of 100mg anakinra 3 hours before the test meal and an oral placebo (winthrop tablet)before the test meal will be administered by an Independent nurse to the blinded patient

    Drug: Anakinra · Other: oral placebo (winthrop tablet)

Interventions

  • DrugEmpagliflozin

    Glucose lowering effect of empagliflozin for reducing the counter-regulatory glucose-lowering response

  • DrugAnakinra

    IL-1Beta blockage effect on insulin secretion and thereby influencing postprandial glucose level

  • Otheroral placebo (winthrop tablet)

    subcutaneous placebo (0.67 ml of 0.9% sodium chloride) 3 hours before the test meal and an oral placebo (winthrop tablet) 2 hours before the test meal will be administered by an Independent nurse to the blinded patient

  • Othersubcutaneous placebo (0.67 ml of 0.9% sodium chloride)

    subcutaneous placebo (0.67 ml of 0.9% sodium chloride) will be administered in arm 'Placebo-Placebo' and arm 'drug: Empagliflozin'

05

What researchers measure

Primary outcomes

  1. Postprandial hypoglycemia in patients after bariatric surgery

    To assess whether empagliflozin or anakinra compared to placebo reduce the severity of hypoglycemia (i.e. change of blood glucose level in mmol/l) following a mixed-meal in patients after bariatric surgery.

    Time frame: 6 hours

Secondary outcomes

  1. change of C-peptide

    plasma level of c-peptide with anakinra or empagliflozin in comparison to placebo

    Time frame: 6 hours

  2. plasma level of IL-1Beta

    plasma level of IL-1Beta with anakinra or empagliflozin in comparison to placebo

    Time frame: 6 hours

  3. plasma level of Glucagon-like Peptide1 (GLP1)

    plasma level of GLP1 with anakinra or empagliflozin in comparison to placebo

    Time frame: 6 hours

  4. change of glucagon level

    plasma level of glucagon with anakinra or empagliflozin in comparison to placebo

    Time frame: 6 hours

  5. changes in Edinburgh Hypoglycemia Scale

    changes in Edinburgh Hypoglycemia Scale with anakinra or empagliflozin in comparison to placebo

    Time frame: 6 hours

  6. amount of glucose needed for restoring normoglycemia

    amount (gramme) of glucose needed for restoring normoglycemia with anakinra or empagliflozin in comparison to placebo

    Time frame: 6 hours

  7. length of time needed for restoring normoglycemia

    length of time (minutes) needed for restoring normoglycemia with anakinra or empagliflozin in comparison to placebo

    Time frame: 6 hours

06

Study locations

1 site
  • University Hospital Basel, Department of Endocrinology, Diabetes and Metabolism
    Basel, 4056 Basel, Switzerland
07

References and documents

Publications

  • Hepprich M, Wiedemann SJ, Schelker BL, Trinh B, Starkle A, Geigges M, Loliger J, Boni-Schnetzler M, Rudofsky G, Donath MY. Postprandial Hypoglycemia in Patients after Gastric Bypass Surgery Is Mediated by Glucose-Induced IL-1beta. Cell Metab. 2020 Apr 7;31(4):699-709.e5. doi: 10.1016/j.cmet.2020.02.013. Epub 2020 Mar 19. PubMed 32197070 ↗

Individual participant data

Plan to share: No

08

Registry details

Key details

Study ID
NCT03200782
Lead sponsor
University Hospital, Basel, Switzerland
Responsible party
Sponsor
First posted
Jun 27, 2017
Start date
May 30, 2017
Primary completion
Sep 21, 2018
Completion
Sep 21, 2018
Last update
Oct 24, 2018

Study contacts

Marc Donath, MD, Prof.
principal investigator · University Hopsital Basel

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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